It is our hypothesis that alcohol abuse leads to the depletion of polyunsaturated lipids from many tissues. Such changes in the liver and brain as well as in other organs and tissues may cause or contribute to the pathological changes associated with alcoholism. Previously, we have shown that there are losses in arachidonic acid (20:4n6) and other n-6 fatty acids in alcohol exposed rat tissues as well as in the blood cells of alcoholics. Animals fed borage oil rich in 18:3n6 during the ethanol inhalation period (7 d), did not have as great a loss in 20:4n6 as those fed 18:1n9 or long chain n-3 fatty acid-based diets and these losses were traced mainly to the phospholipid and cholesterol ester pools. Similarly, losses in n-3 fatty acids subsequent to alcohol exposure were not as great in animals fed a menhaden oil-based diet. The rodent model of alcoholism has been improved with the use of 12 hr per day of inhalation rather than continuous exposure, a longer duration of exposure and the control of the diets, particularly with low essential fat formulation. Human studies have shown that our species are capable of a complete spectrum of essential fatty acid metabolism and that polyunsaturates in the diet regulate the activity of this pathway.